We will investigate the utilization of platinum group metal coordination complexes as a new class of potent antitumor agents. This will include basic and applied categories of study as follows: 1. Syntheses, purification and characterization of a large number of complexes, particularly those with pyrimidine, purine and amino acid ligands attached to the metal, and various amine groups trans to these ligands. 2. We will determine the rules governing the structure-activity relations. 3. We will study the interactions of the 'Platinum-Pyrimidine Blues' and related complexes with nucleic acids and model systems (polynucleotides, mono-, di-, and triphosphates of nucleotides). 4. We will investigate electron microscopy of cells stained with these complexes to determine the nature of the densely stained aggregates (most likely DNA) on the membrane surface of tumorigenic cells which do not appear in normal cells; its potential as a diagnostic tool; and its possible relevance to tumorigenicity. 5. We will develop treatment regimens for use of these drugs which decrease kidney toxicity and enhance therapeutic efficacy. 6. We will continue our studies on the hypothesis that drug induced tumor regressions are mediated via immunologic mechanisms of the host ('enhanced antigenicity') rather than specific cytotoxic attack on tumor cells.